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@ARTICLE{Siddiqui:259000,
      author       = {Siddiqui, Tohid and Cosacak, Mehmet Ilyas and Popova,
                      Stanislava and Bhattarai, Prabesh and Yilmaz, Elanur and
                      Lee, Annie J and Min, Yuhao and Wang, Xue and Allen, Mariet
                      and İş, Özkan and Atasavum, Zeynep Tansu and
                      Rodriguez-Muela, Natalia and Vardarajan, Badri N and
                      Flaherty, Delaney and Teich, Andrew F and Santa-Maria,
                      Ismael and Freudenberg, Uwe and Werner, Carsten and Tosto,
                      Giuseppe and Mayeux, Richard and Ertekin-Taner, Nilüfer and
                      Kizil, Caghan},
      title        = {{N}erve growth factor receptor ({N}gfr) induces neurogenic
                      plasticity by suppressing reactive astroglial
                      {L}cn2/{S}lc22a17 signaling in {A}lzheimer's disease.},
      journal      = {npj regenerative medicine},
      volume       = {8},
      number       = {1},
      issn         = {2057-3995},
      address      = {[London]},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2023-00713},
      pages        = {33},
      year         = {2023},
      abstract     = {Neurogenesis, crucial for brain resilience, is reduced in
                      Alzheimer's disease (AD) that induces astroglial reactivity
                      at the expense of the pro-neurogenic potential, and
                      restoring neurogenesis could counteract neurodegenerative
                      pathology. However, the molecular mechanisms promoting
                      pro-neurogenic astroglial fate despite AD pathology are
                      unknown. In this study, we used APP/PS1dE9 mouse model and
                      induced Nerve growth factor receptor (Ngfr) expression in
                      the hippocampus. Ngfr, which promotes neurogenic fate of
                      astroglia during the amyloid pathology-induced
                      neuroregeneration in zebrafish brain, stimulated
                      proliferative and neurogenic outcomes. Histological analyses
                      of the changes in proliferation and neurogenesis,
                      single-cell transcriptomics, spatial proteomics, and
                      functional knockdown studies showed that the induced
                      expression of Ngfr reduced the reactive astrocyte marker
                      Lipocalin-2 (Lcn2), which we found was sufficient to reduce
                      neurogenesis in astroglia. Anti-neurogenic effects of Lcn2
                      was mediated by Slc22a17, blockage of which recapitulated
                      the pro-neurogenicity by Ngfr. Long-term Ngfr expression
                      reduced amyloid plaques and Tau phosphorylation. Postmortem
                      human AD hippocampi and 3D human astroglial cultures showed
                      elevated LCN2 levels correlate with reactive gliosis and
                      reduced neurogenesis. Comparing transcriptional changes in
                      mouse, zebrafish, and human AD brains for cell intrinsic
                      differential gene expression and weighted gene co-expression
                      networks revealed common altered downstream effectors of
                      NGFR signaling, such as PFKP, which can enhance
                      proliferation and neurogenesis in vitro when blocked. Our
                      study suggests that the reactive non-neurogenic astroglia in
                      AD can be coaxed to a pro-neurogenic fate and AD pathology
                      can be alleviated with Ngfr. We suggest that enhancing
                      pro-neurogenic astroglial fate may have therapeutic
                      ramifications in AD.},
      cin          = {AG Kizil / AG Rodriguez-Muela},
      ddc          = {610},
      cid          = {I:(DE-2719)1710007 / I:(DE-2719)1713001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10333226},
      pubmed       = {pmid:37429840},
      doi          = {10.1038/s41536-023-00311-5},
      url          = {https://pub.dzne.de/record/259000},
}